Clinical pharmacokinetics of etintidine

The pharmacokinetics of etintidine (E), a potent H2 blocker, were studied in 12 normal, fasted subjects. The subjects received five ascending doses of E HCl in capsules at 72-h intervals. Blood and urine samples were collected and the plasma and urine levels of E were determined by HPLC. Following oral administration, plasma E levels showed double peaks in half of the subjects. Mean Cmax (0.42, 2.11, 3.82, 4.50, and 7.15 micrograms ml-1), AUC0-infinity (0.96, 4.94, 11.3, 17.5, and 24.5 h micrograms ml-1), and the amount of E excreted unchanged in 72 h (20, 54.8, 170, 320, and 371 mg) were determined. These parameters indicate the amount of E absorbed increased linearly with dose for each individual. Renal clearance was independent of the dose and the mean value (16.6 lh-1) was about twice that of the creatinine clearance (which did not significantly change as a result of E treatment), indicating that E is actively secreted into the renal tubules. As E was eliminated rapidly from the body (t1/2 less than 2 h), no substantial accumulation of E is expected after multiple dose treatment.